Evidence that enviroxime targets multiple components of the rhinovirus 14 replication complex

Evidence that enviroxime targets multiple components of the rhinovirus 14 replication complex Enviroxime and related analogs are potent inhibitors of rhinoviruses and enteroviruses in cell culture. Previous analyses of resistant mutants implicated the viral nonstructural protein 3A(B) as the likely target of drug activity. In this study, we used site-directed mutagenesis and selection of spontaneous rhinovirus 14 mutants with several enviroxime analogs to confirm the link between domains in rhinovirus 14 3A(B) and the function blocked by enviroxime. We also produced recombinant 3A and 3AB proteins for biochemical analyses. Despite extensive efforts, however, we were unable to demonstrate direct binding between enviroxime and any of several viral proteins, nor could we demonstrate binding of enviroxime to a host protein. In addition, enviroxime did not disrupt 3AB's ability to bind RNA or 3D polypeptide, the association of 3AB with membranes, or the cleavage of 3AB by 3C protease. Finally, we identified an enviroxime-resistant mutant with an increased level of resistance which apparently has mutations in multiple proteins or RNA sequences. Taken together, these results suggest that enviroxime targets a complex of proteins and/or cellular factors. Such a complex mechanism of inhibition might explain the low levels of viral resistance to these inhibitors as compared with other picornaviral inhibitors. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Evidence that enviroxime targets multiple components of the rhinovirus 14 replication complex

Loading next page...
 
/lp/springer_journal/evidence-that-enviroxime-targets-multiple-components-of-the-rhinovirus-vbPJfMzwlo
Publisher
Springer-Verlag
Copyright
Copyright © Wien by 1999 Springer-Verlag/
Subject
Legacy
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s007050050611
Publisher site
See Article on Publisher Site

Abstract

Enviroxime and related analogs are potent inhibitors of rhinoviruses and enteroviruses in cell culture. Previous analyses of resistant mutants implicated the viral nonstructural protein 3A(B) as the likely target of drug activity. In this study, we used site-directed mutagenesis and selection of spontaneous rhinovirus 14 mutants with several enviroxime analogs to confirm the link between domains in rhinovirus 14 3A(B) and the function blocked by enviroxime. We also produced recombinant 3A and 3AB proteins for biochemical analyses. Despite extensive efforts, however, we were unable to demonstrate direct binding between enviroxime and any of several viral proteins, nor could we demonstrate binding of enviroxime to a host protein. In addition, enviroxime did not disrupt 3AB's ability to bind RNA or 3D polypeptide, the association of 3AB with membranes, or the cleavage of 3AB by 3C protease. Finally, we identified an enviroxime-resistant mutant with an increased level of resistance which apparently has mutations in multiple proteins or RNA sequences. Taken together, these results suggest that enviroxime targets a complex of proteins and/or cellular factors. Such a complex mechanism of inhibition might explain the low levels of viral resistance to these inhibitors as compared with other picornaviral inhibitors.

Journal

Archives of VirologySpringer Journals

Published: Aug 1, 1999

There are no references for this article.

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve Freelancer

DeepDyve Pro

Price
FREE
$49/month

$360/year
Save searches from
Google Scholar,
PubMed
Create lists to
organize your research
Export lists, citations
Read DeepDyve articles
Abstract access only
Unlimited access to over
18 million full-text articles
Print
20 pages/month
PDF Discount
20% off